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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04246489




Registration number
NCT04246489
Ethics application status
Date submitted
28/01/2020
Date registered
29/01/2020
Date last updated
2/07/2020

Titles & IDs
Public title
Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer
Scientific title
A Phase II, Multicenter, Open Label Study of Bintrafusp Alfa (M7824) Monotherapy in Participants With Advanced, Unresectable Cervical Cancer With Disease Progression During or After Platinum-Containing Chemotherapy
Secondary ID [1] 0 0
2019-003583-40
Secondary ID [2] 0 0
MS200647_0017
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uterine Cervical Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Cervical (cervix)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bintrafusp alfa

Experimental: Bintrafusp alfa -


Treatment: Drugs: Bintrafusp alfa
Participants will receive an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, death, unacceptable toxicity and study withdrawal.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Confirmed Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) as Evaluated by Independent Review Committee
Timepoint [1] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [1] 0 0
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
Timepoint [1] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [2] 0 0
Durable Response of at Least 6 Months According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
Timepoint [2] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [3] 0 0
Occurrence of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related AEs, Including Adverse Events of Special Interest (AESIs)
Timepoint [3] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [4] 0 0
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
Timepoint [4] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [5] 0 0
Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
Timepoint [5] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [6] 0 0
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
Timepoint [6] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [7] 0 0
Durable Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
Timepoint [7] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [8] 0 0
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
Timepoint [8] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [9] 0 0
Overall Survival (OS)
Timepoint [9] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [10] 0 0
Concentration of M7824 at the end of Infusion (Ceoi)
Timepoint [10] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [11] 0 0
Concentration of M7824 at the end of the Dosing Interval (C trough)
Timepoint [11] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [12] 0 0
Immunogenicity as measured by Anti-drug Antibodies Concentration
Timepoint [12] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [13] 0 0
Confirmed Objective Response According to RECIST Version 1.1 Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression
Timepoint [13] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [14] 0 0
Duration of Response (DOR) According to (RECIST Version 1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression
Timepoint [14] 0 0
Time from first treatment to planned final assessment at approximately 2 years
Secondary outcome [15] 0 0
Durable Response According to RECIST Version 1.1 Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression
Timepoint [15] 0 0
Time from first treatment to planned final assessment at approximately 2 years

Eligibility
Key inclusion criteria
- Participants have advanced unresectable and/or metastatic cervical cancer (squamous
cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma) with disease progression
during or after the prior platinum-containing chemotherapy:

1. The prior platinum-containing chemotherapy may be a systemic treatment for
metastatic disease or in the adjuvant or neo-adjuvant setting.

2. Participants who were intolerant to or ineligible for platinum-based chemotherapy
are also eligible.

3. Participants must be naïve to checkpoint inhibitors

- Participants must have measurable disease.

- Participants must provide a tumor tissue sample, either from archival tissue or newly
obtained core or excisional biopsy. If the participant received local therapy (For
example: radiation therapy or chemoradiotherapy) after the archival tissue was taken,
a new biopsy will be required.

- Participants who have Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1

- Life expectancy greater than or equals to (>=) 12 weeks as judged by the Investigator

- Adequate hematological, hepatic and renal function as defined in the protocol

- Participants with known Human Immunodeficiency Virus (HIV) infections are in general
eligible if the following criteria are met:

1. Clinically indicated participants must be stable on antiretroviral therapy (ART)
for at least 4 weeks and agree to adhere to ART.

2. have no evidence of documented multi-drug resistance that would prevent effective
ART.

3. Have an HIV viral load of < 400 copies per milliliter (/mL) at Screening.

4. Have CD4+ T-cell (CD4+) counts >= 350 cells/microliter.

5. For participants with a history of an Acquired immunodeficiency syndrome
(AIDS)-defining opportunistic infection within the last 12 months, participants
may be eligible only after consultation and agreement with the study Medical
Monitor.

6. If prophylactic antimicrobial drugs are indicated, participants may still be
considered eligible upon agreement with the study Medical Monitor

- Participants with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections
are in general eligible if the following criteria are met:

1. HBV viral load below the limit of quantification and be on a stable dose of
antiviral therapy.

2. Participants with a history of HCV infection should have completed curative
antiviral treatment and require HCV viral load below the limit of quantification.

3. Participants on concurrent HCV treatment should have HCV below the limit of
quantification

- Other protocol defined inclusion criteria could apply
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants with active central nervous system (CNS) metastases causing clinical
symptoms or require therapeutic intervention are excluded. Participants with a history
of treated CNS metastases (by surgery or radiation therapy) are not eligible unless
they have fully recovered from treatment, demonstrated no progression for at least 4
weeks, and are not using steroids for at least 7 days prior to the start of study
treatment.

- Participants with interstitial lung disease or has had a history of pneumonitis that
has required oral or intravenous (IV) steroids

- Participants with significant acute or chronic infections

- Participants with active autoimmune disease that might deteriorate when receiving an
immunostimulatory agent

- Participants with clinically significant cardiovascular/cerebrovascular disease
including: cerebral vascular accident/stroke, myocardial infarction, unstable angina,
congestive heart failure, or serious cardiac arrhythmia

- Other protocol defined exclusion criteria could apply

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre-East Melbourne - Melbourne
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment postcode(s) [3] 0 0
- Nedlands
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Nevada
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
Argentina
State/province [16] 0 0
Santa Fe
Country [17] 0 0
Argentina
State/province [17] 0 0
Salta
Country [18] 0 0
Argentina
State/province [18] 0 0
Tucuman
Country [19] 0 0
Belgium
State/province [19] 0 0
Bruxelles
Country [20] 0 0
Belgium
State/province [20] 0 0
Gent
Country [21] 0 0
Belgium
State/province [21] 0 0
Kortrijk
Country [22] 0 0
Belgium
State/province [22] 0 0
Libramont
Country [23] 0 0
Belgium
State/province [23] 0 0
Liège
Country [24] 0 0
Belgium
State/province [24] 0 0
Pellenberg
Country [25] 0 0
Belgium
State/province [25] 0 0
Wilrijk
Country [26] 0 0
Brazil
State/province [26] 0 0
Rio Grande Do Sul
Country [27] 0 0
Brazil
State/province [27] 0 0
São Paulo
Country [28] 0 0
China
State/province [28] 0 0
Chongqing
Country [29] 0 0
China
State/province [29] 0 0
Hubei
Country [30] 0 0
China
State/province [30] 0 0
Shanghai
Country [31] 0 0
China
State/province [31] 0 0
Guangzhou
Country [32] 0 0
France
State/province [32] 0 0
Alpes Maritimes
Country [33] 0 0
France
State/province [33] 0 0
Bas Rhin
Country [34] 0 0
France
State/province [34] 0 0
Cotes d'Armor
Country [35] 0 0
France
State/province [35] 0 0
Nord
Country [36] 0 0
France
State/province [36] 0 0
Bordeaux cedex
Country [37] 0 0
France
State/province [37] 0 0
Lyon
Country [38] 0 0
France
State/province [38] 0 0
Marne
Country [39] 0 0
France
State/province [39] 0 0
Paris
Country [40] 0 0
France
State/province [40] 0 0
Pierre Benite cedex
Country [41] 0 0
France
State/province [41] 0 0
Saint Herblain
Country [42] 0 0
Hungary
State/province [42] 0 0
Budapest
Country [43] 0 0
Hungary
State/province [43] 0 0
Debrecen
Country [44] 0 0
Hungary
State/province [44] 0 0
Kecskemet
Country [45] 0 0
Hungary
State/province [45] 0 0
Nyiregyhaza
Country [46] 0 0
Japan
State/province [46] 0 0
Fukuoka-Ken
Country [47] 0 0
Japan
State/province [47] 0 0
Okinawa-Ken
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka-Fu
Country [49] 0 0
Japan
State/province [49] 0 0
Saitama-Ken
Country [50] 0 0
Japan
State/province [50] 0 0
Tokyo-To
Country [51] 0 0
Japan
State/province [51] 0 0
Kurume-shi
Country [52] 0 0
Japan
State/province [52] 0 0
Sapporo-shi
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Gyeonggi-do
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Seoul
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Suwon
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Chelyabinsk
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Krasnodar
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Omsk
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Pyatigorsk
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Saint Petersburg
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Saint-Petersburg
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Girona
Country [64] 0 0
Spain
State/province [64] 0 0
Madrid
Country [65] 0 0
Spain
State/province [65] 0 0
Málaga
Country [66] 0 0
Spain
State/province [66] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The main purpose of this study is to evaluate clinical efficacy and safety of bintrafusp alfa
in participants with advanced, unresectable cervical cancer with disease progression during
or after platinum-containing chemotherapy.
Trial website
https://clinicaltrials.gov/show/NCT04246489
Trial related presentations / publications
Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marté JL, Donahue RN, Grenga I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL. Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFß, in Advanced Solid Tumors. Clin Cancer Res. 2018 Mar 15;24(6):1287-1295. doi: 10.1158/1078-0432.CCR-17-2653. Epub 2018 Jan 3.
Lan Y, Zhang D, Xu C, Hance KW, Marelli B, Qi J, Yu H, Qin G, Sircar A, Hernández VM, Jenkins MH, Fontana RE, Deshpande A, Locke G, Sabzevari H, Radvanyi L, Lo KM. Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-ß. Sci Transl Med. 2018 Jan 17;10(424). pii: eaan5488. doi: 10.1126/scitranslmed.aan5488.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US Medical Information
Address 0 0
Country 0 0
Phone 0 0
888-275-7376
Fax 0 0
Email 0 0
eMediUSA@emdserono.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04246489